Hello everyone, welcome to the Faron Pharmaceuticals ESMO 2025 webcast. My name is Juho Jalkanen, I'm the Chief Executive Officer of Faron Pharmaceuticals. We are extremely happy to bring you our latest data from ESMO. Let's go to the next slide, please. As you may know, we really want to serve the public, so here with me today we have the actual presentation from ESMO, and the presenter will be Dr. Mika Kontrö, our Principal Investigator from the University Hospital of Helsinki. After that, our Chief Medical Officer, Dr. Petri Bono, will talk more about what do these findings actually mean and what are the implications of these findings. He will also further address our development program going further. I will then, at the end, wrap up, also give a business update, and then at the end, there will be a Q&A, and during the webcast, you can type in your questions to be answered at the end. Great to have you all here, and I'll give the stage to Dr. Mika Kontrö. Thank you, Juho. I will present the presentation I gave at ESMO on behalf of my co-authors, where we showed the data on bexmarilimab plus azacitidine in myelodysplastic syndromes. Next. Here are my disclosures, and next. Clever-1 is a novel macrophage immune checkpoint. Inhibition of Clever-1 with bexmarilimab converts antitumorigenic macrophages to pro-inflammatory ones and also activates T-cell responses. In MDS, bexmarilimab also targets blast cell energy production. In the first stage of the trial, the patients received a combination of azacitidine plus bexmarilimab. The dose escalation was guided by point design, and we explored 1, 3, and 6 milligrams per kilogram dose levels. Bexmarilimab was dosed weekly. The trial recruited treatment-naive MDS with intermediate, high, or very high risk IPSS score. It also included patients that had failed their previous HMA therapy, patients with MDS and CMML. For dose optimization in the phase 2 part of the trial, HMA-failed patients were randomized to receive either 6 milligrams or 3 milligrams per kilogram bexmarilimab in combination with azacitidine in line with the PREGOPTIMUS design. Next slide, please. The trial recruited altogether 21 treatment-naive MDS patients and 32 HMA-failed MDS patients. Let's first concentrate on the treatment-naive patient population. As you can see, over 50% of the patients had a high or very high risk of disease as defined by IPSS-R. TP53 mutations were prevalent, and they were observed in 43% of the treatment-naive MDS patients. 38% of these treatment-naive MDS patients had a low blast count at baseline. When looking at HMA-failed patient population, again, high and very high risk disease were prevalent in the patient population, and TP53 mutations were observed in 41% of the patients. Importantly, I want to underline that altogether one-third of the patients had a previous venetoclax therapy. When looking at safety on the right-hand panel, first of all, we can state that azacitidine in combination with bexmarilimab was well tolerated. Febrile neutropenia was observed in 28% of the patients. Altogether, 36% of the patients had bexmarilimab-related adverse events, most commonly being leukopenia and neutropenia. Importantly, we did not witness any grade 5 bexmarilimab-related AEs. Next slide. When looking at efficacy for treatment-naive patient population, we had 20 available patients. The complete remission rate defined by 2006 criteria was 45%. Regarding TP53-mutated patients, responses were observed in 78% of the treatment-naive patients, and for HMA-failed patients, the corresponding number was 46%. For treatment-naive patients with low baseline blast count, actually all patients achieved treatment response. When looking at the waterfall plot on the right-hand side, altogether 55% of the treatment-naive MDS patients showed a full clearance of bone marrow blasts. I should underline here that actually 23% of the trial participants were bridged to allogeneic transplantation, and currently, the median overall survival estimate for HMA-failed patient population is 13.4 months. Next slide, please. The PK profile of bexmarilimab is very typical for monoclonal antibody. It's super dose proportional, and it's nonlinear. Importantly, we observed little or no accumulation of bexmarilimab with weekly dosing. We observed target engagement, which is shown on the right-hand side, with all those levels in the bone marrow. Next slide. We also observed significantly better bone marrow target engagement in responding patients, which was clearly demonstrated in the patient population with low bone marrow blast count at baseline. Next slide. To summarize, first of all, the combination of azacitidine plus bexmarilimab has shown a tolerable safety profile. Regarding efficacy, we see good responses in both frontline patient population and also HMA-failed patient population. Importantly, we were capable of bridging 23% of the trial participants to allogeneic transplantation. Regarding biomarkers, we observed higher target engagement in responding patients, and this was clearly demonstrated in patients with low blast count at baseline. Next slide. Okay, my acknowledgement slide is missing, but of course, I want to thank here all the patients and their families for trial participation, our excellent trial teams across the U.S., UK, and Finland, and also the Faron team for supporting the trial. Thank you. Thank you, Mika. Yes. About key learnings from ESMO and also about the way forward from here, could I get the next slide, please? My name is Petri Bono, Chief Medical Officer at Faron Pharmaceuticals. Targeting Clever-1 in myeloid malignancies, what are the benefits of bexmarilimab here? Actually, we do have several different modes of action shown here. Most importantly, immune activation via monocytes and macrophages, leading to antigen presentation and increased T-cell infiltration. Second one, apoptotic priming of blast cells via impaired mitochondrial metabolism, meaning that the actual blast cells are not feeling so good when treated with Bex, and this leads to that they are sensitized to the standard of care such as azacitidine. Finally, a new one, increased hematopoiesis by targeting progenitor cell activity, which leads to faster hematological recovery, and on the other hand, also better tolerability of the combination treatment. A couple of slides in the next ones about these modes of action a little bit more in detail. Could I get the next slide, please? The multiple ways Bex works in myeloid malignancies, on the left first, macrophage activation, and this is very important. This leads to this macrophage activation to increased antigen presentation shown on the right part of the slide with increased HLA-DR expression. You can see that increase in the monocyte antigen presentation and higher with patients who respond to treatment. This is data taken from phase one Lancet Hematology paper published earlier this year by Dr. Mika Kontrö and his colleagues. On the right one, you can see that the CD4 positive T-cell numbers, as an example, CD8 positive T-cells behave exactly similarly, so that the increase in the number of infiltrated T-cells in the bone marrow biopsies. Very importantly, we impair mitochondrial metabolism and impair the lipid metabolism there, and this leads to the sensitization of these blast cells to our agent Bex. Next slide, please. This is what is this increased hematopoiesis, how that has been shown. The problem with many agents that have been combined in the treatment of MDS together with azacitidine has been that they've been toxic, they've been myelosuppressive, and lots of side effects have led to early discontinuation of treatment or to suboptimal dose intensity with AZA. With Bex, we can actually see that we can increase the number of progenitor cells of erythrocyte, leukocytes, and platelets shown here in patients that have been treated in BEXMAB trial and analyzed by single-cell RNA sequencing technique. On the right side, the red circle shows the increase in these progenitor cells, and at the same time, we can see on the left red circle a decrease in the immunosuppressive cells and also a decrease in the TGF-beta high expressing cells. Everything pointing out towards removal of immunosuppression and also towards increasing hematopoiesis. Next slide, please. This is about the safety that has been one of the main reasons that other assets have failed in MDS. In this slide, you can see from three different agents in gray. These include venetoclax, anti-CD47 antibody magrolimab, anti-T3 antibody sabatolimab, and then our Bex in orange color. If we have a look at the grade 3 to 4 treatment-related adverse events or drug withdrawals due to drug-related adverse events or rates of leukopenia, neutropenia, thrombocytopenia, anemia, or pneumonia, we can see in our BEXMAB trial the absolute number of these has been significantly lower than what has been observed in these other trials with these failed assets that were combined with azacitidine similarly as our Bex has been combined with azacitidine. Clearly, Bex is demonstrating a better safety profile with this potential for hematological recovery. Next slide, please. The contribution of Bex. We are treating patients with a combination of azacitidine and Bex, and the contribution of either agent without a direct randomized study is actually not possible. This data shown here, that is the target engagement and the difference between responders and non-responders, this is best that one can get without a randomized setting. On the left side of the slide, in green responders and in yellow non-responders, we can see that there's a significant difference between the bone marrow target engagement so that the responding patients have higher target engagement than the non-responders. This was done by measuring soluble Clever-1 in the bone marrow samples, and also can be seen on the right side, similar finding when we split with the same technique the responders between complete remission patients or CR patients, other kind of responders, and then in green one, no-response patients. There's a very nice linear correlation between the target engagement and response so that the highest target engagement there on the left side of the slide is with the ones who got complete remission and the lowest with the ones with no response. Next slide, please. Why is this then important? What Mika already told, actually we have significantly better bone marrow target engagement in responding patients who have, especially who have less than 5% blast counts. This is important because with many agents, these patients have been difficult to treat in the combination trials. One such is venetoclax that was recently the results of phase 3 venetoclax-associated results were recently published. This, and there venetoclax didn't work with patients less than 5% blasts, and it seems to work best with patients with more than 10% baseline blast counts. At the same time, trial prevalence of these patients who have less than 5% baseline blast seems to be increasing in recent years and actually may have contributed to some of the trial failures. As has been shown in Mika's presentation, we had 100% overall response rate among these less than 5% blast patients. We can clearly see that we have activity also in these difficult to treat less than 5% patients. The evolution of the MDS classification and blast distribution can be shown in this slide also. It seems to be really that less than 10% blasts are dominating in newer trials, and our results did different in the target engagement remains the same if we use 10% as the cutoff for the baseline blast count. There you can see the numbers: these less than 10% blasts, Verona 63%, magrolimab 33% less than 5, and in our BEXMAB 40% less than 5. Next slide, please. If we go back to patient level, what does it mean? This is a case study as an example of a patient with low blast count when entering the trial, treatment-naive patient, very complex karyotype. This patient with Bex AZA reaches full disease clearance and for full CR. So 66-year patient from the U.S., 4% blast in bone marrow, high risk score, biallelic TP53 mutant, check kinase mutant, and seven different chromosomal abnormalities indicating a complex karyotype. After already two cycles of Bex treatment, none of abnormalities, just one, and after end of cycle three, no more abnormalities. Importantly, not just a decline in the number of the bone marrow blasts, but also improvement in the blood values. There you can see that the number of platelets in yellow, hemoglobin in purple, and neutrophils in blue, they all pass the CR limit, meaning normalization of these blood values and indicating that this difficult to treat patient with the complex karyotype has received a full CR or, according to the new criteria, CR equivalent. Next slide, please. How to move forward. BEXMAB trial phase 2 results now presented at ESMO as an oral presentation. We had this FDA end of phase 2 meeting mid-August. Where we presented the study plan for the registration trial for higher-risk MDS patients, which will be a phase 2/3 trial, randomized, double-blind, placebo-controlled trial with, very importantly, resizing opportunity to increase the likelihood of success. The running phase, 40+ 40 + 40 patients, placebo, Bex 1 mg per kilo, Bex 3 mg per kilo. After that, unblinded analysis with 120 patients, then the recommended phase 3 dose will continue. No stop will be needed for the enrollment in the trial. Thereafter, patients will be randomized between placebo AZA and Bex randomized phase 2 dose AZA. The size of the trial, 428 patients, final overall survival analysis with them. Very importantly, interim analysis also for the survival where there's a possibility for resizing. The trial will have two primary endpoints. The first one, CR plus CR equivalent rate, and the second one will be overall survival. The first analysis of the CR plus CR equivalent, so that will be there after these 254 patients have been treated either with Bex AZA or placebo AZA. There's an accelerated approval possibility based on that interim readout, and that's something that was aligned also with FDA in their meeting. The survival analysis, or final survival analysis, will then come later when there are a sufficient number of events for survival or a sufficient number, unfortunately, for deaths that are required by the protocol for the final survival analysis. Next slide, please. About further development pipeline, this was the registrational phase 2/3 trial I explained. We call it BexNOVA, and the protocol preparations and practical preparations are nicely ongoing with that one. In blue, you can see in this slide also some other trials that we've been working hard throughout 2025. There's anticipated also for some key milestones on the right side here. Happy to tell that we are on track with all of these. The BLASE one, that will be PD-1 inhibitor plus Bex in PD-1-resistant lung cancer and melanoma patients through a master in the UK. We are on track to expect first patient in still at the end of the year. Protocol is fully ready and just waiting to get the trial started now. Soft tissue sarcomas, that's a trial where protocol is fully ready. Practicalities are ongoing that are required to start the trial in H1 2026. Sarcomas are, after AML and MDS, the highest expressing tumor type for Clever-1, the target. Very importantly, it's not single agent, it's together with chemo, doxorubicin, that is a standard of care for first-line sarcoma patients. We are working hard to get breast cancer trial in frontline chemo combination, and that will be for Clever-1 positive breast cancer patients. We are on track to get first patient in in H1 2026, but some more work needed still to finalize that we can start enrolling Finnish-based breast cancer patients to the trial. The final one is a company-sponsored basket trial, but those activities won't start before we see signal from these three proof of concept solid tumor combination trials. I think next slide is already back to Juho. Thank you, Petri. Before we go into business, I would just like to conclude or wrap up all that data that Mika and Petri went over. Thank you, gentlemen. To me, what this means is that with this low blast count population where the disease resides mainly in the bone marrow, it's very hard to hit that disease with classical toxic tumor killing agents. Bexmarilimab, as a truly disease-modifying agent, which actually has very good bone marrow penetration, will actually work on the core biology of the disease. We believe we are the first drugs to actually drill down on this reason on why MDS and possibly AML are such difficult diseases to treat. We can really get rid of them even though when the disease is mainly still hiding in the bone marrow. That is what was highlighted with the patient case Petri presented, that not a lot of cancer, but very bad cancer in the bone marrow, so that complex karyotype means a lot of mutations, bad mutations. We can really be clearing out that. Bex, again, is a truly disease-modifying agent. Now the business, some of you may be thinking, why is Juho presenting a survival curve from the Matthews trial? As you may have come accustomed to, we're very transparent in our goals and aims and what we want to achieve. You also are very familiar that we've been extremely busy on the business front since we received that FDA feedback at the end of phase 2 meeting. A lot of these business activities are coming to their end. We will hopefully soon be coming out. I know a lot of you are eager waiting on what is the business activities resulting in. This is why I bring again this melanoma data from the Matthews trial, showing that in deeply cold immunosuppressive non-responsive tumors, Bexmarilimab, even as a single agent, can have a dramatic survival benefit. Bexmarilimab is the only macrophage checkpoint inhibitor that has shown anything like this in solid tumors. That's why we believe Bex has huge potential in a number of very difficult to treat cancers, not just MDS. We, as a company, what we need to deliver for patients, mankind, solely focused on getting the resources, the activities going for the registrational MDS trial to get this drug approved. Meanwhile, also proving the concept of Bex can overcome treatment resistance in a number of cancers, so we can benefit possibly a huge number of cancer patients. While we do these business activities, we want to see that Faron shareholders will benefit from this broader application of Bex and benefiting an extremely big number of cancer patients. That's what we aim to bring to you. When we come out, have an eye on that, how did we deliver? Next, we'll be going to the Q&A. Moderating the Q&A, we have our Chief Business Officer, Rafe Hughes. Thank you, Juho, and yes, lovely to meet you all. I'm Rafe Hughes, Chief Business Officer. We'll just fire straight away with some questions. I think the first question we'll go for is, and I think this is probably for you, Petri, can you talk more about the significance of the translational data that you showed? What is the implication of seeing higher response in patients who showed bone marrow engagement while both groups are treated with azacitidine? What's the significance of that translational data? Yes, thanks, Rafe. Great question. Really, since both groups were treated with azacitidine plus bexmarilimab, you can see the difference in the target engagement between responders and non-responders shows the contribution of bexmarilimab to the combination. This is important. This is also something that regulatory agencies are always interested in, that when you're having combination treatment, what's the contribution of the novel agent. In this single arm trial that we have run, this is the most beautiful data that can be shown to really convince that it's the bexmarilimab that is contributing to the efficacy and to the responses. This is, to me, the most important message from this one. Thank you, Petri. A couple more questions here on blasts. Could you remind us of the blast% influence responses, and can you expand on what was observed in venetoclax population in the low blast count patients? I think you mentioned something earlier, but you know how did that have an impact? Yeah. Bex azacitidine has good efficacy among less than 5% blast count patients and higher than 5%. Mika showed in one of his slides that the response rate was 100% in those less than 5% treatment naive patients and 75% in more than 5%. The difference is not statistically significant, but the 100% response rate in those low blast count patients really shows that we have very good efficacy among those patients, why it's important. For example, in the recent phase 3 venetoclax trial that was unfortunately negative, that has been a shock to the field in general. In that one, in a subgroup analysis that was shown in the SOHO meeting in September, venetoclax was beneficial only for higher blast count patients who have over 10% and didn't seem to work at all for the ones who have less than 5% blast counts. Our mode of action is completely different. Venetoclax is a BCL-2 inhibitor. We have several modes of action, and we are an immuno-oncological agent, and we see activity also among the low blast count patients. May I perhaps comment on the top of Petri? As Petri mentioned, the Verona trial was a negative one, and it seems that it was mostly driven by the patients with low blast count. It basically makes sense because these patients, the IPSS-R score, it includes the blood counts, bone marrow blast count, and cytogenetics. The patients that have a normal blast count and have a high IPSS score, they have very low counts. The combination of azacitidine plus venetoclax in this kind of myelosuppressive compartment, it's actually very difficult to treat. In that sense, I think that the data that Petri presented on bexmarilimab's effect on myelopoiesis and supporting blood cell production, it's actually quite promising. Perhaps that's one of the reasons that we see these higher responses in this low blast cell patient population. That perhaps is also the reason why venetoclax failed in that patient population. Exactly. If I may, Rafe, still continue one comment. The increased hematopoiesis may also be here important, as Mika mentioned. We have shown in mice that when we give chemotherapy, 5-fluorouracil to mice, the mice recover a lot faster when they are treated with Bex or if we treat Clever-1 knockout mice with chemotherapy. It's really pointing out towards the better hematopoiesis by inhibition of Bex or by knocking it out in mice. Perfect. Thank you. Let's move on now to, I have a question for you, actually, Mika. What are the plans for AML in Nordics and Figter? Mika, you talked about that. Maybe you could say a little bit more about that. I know the team are working hard to pull something together. Yeah, so the question was for AML in Nordic setting? That's right, yeah. Yeah. So what we currently are planning together with the Nordic AML group, we are planning a trial for AML patients that have an increased MRD, minimal residual disease after allogeneic transplantation. Very briefly, even though we have so many targeted agents for AML, still most patients will be allotransplanted. Allogeneic transplantation is a curative option for higher risk patient population, at least part of the intermediate risk patient population. Unfortunately, it's not curative in a sense that all patients would be cured after allotransplant. The major hurdle for that is the MRD and later on morphological relapses after allogeneic transplantation. What we are currently working on in the Nordic AML group, we are planning a trial for MRD eraser after allotransplant in combination with bexmarilimab, azacitidine, and low dose venetoclax. That's great. Thank you so much. I think linked to that, obviously, we've seen this low blast count, this low blast count data, which obviously indicates that it might work well in that population. Perhaps then also, Juho, this is a question for you. Someone's asked, are there any plans for low risk MDS trials with Bex when funding allows or through partnering? An interesting follow-up, I think, to that low blast count question. Yes, that's an excellent point. We've been thinking a lot about it and discussing with KOLs and Mika as well. With this biology we're seeing, it could be actually a very good drug also for low risk. Low risk, though, is usually well managed. Patients don't come in that often. It's not an aggressive disease. We dose every weekly. Would they come in for a weekly dose? Perhaps again in low risk, even once a month, getting Bex could be enough to keep the disease at bay and make the bone marrow healthier again. Definitely with this biology, it has great promise, I would say, in low risk as well. I would actually like to hear Mika's thinking. Thank you, Juho. As I mentioned, this is a very interesting opening for low-risk MDS patient population, which actually there hasn't been progress for that patient population, apart from basically growth factors for quite a long time. I totally agree that the problem is that what is kind of the optimal dosing? For that patient population, we certainly would need to explore alternative dosing regimens, perhaps not weekly, perhaps every four weeks or every six weeks and so on. I think that's very interesting, and of course, very eager to see the data from the phase 3 trial first, and then perhaps at that point continue on that direction. Perfect. One more question then. What are your current plans to expand secreted Clever-1 in clinical trials? We've seen a lot of interesting data coming out over that. I don't know if that's Petri or Juho, but perhaps something on S-Clever-1? Maybe I'll start and Petri can chime in. What we've seen with soluble Clever-1, and this is what these Clever-1 positive macrophages secrete, is that soluble Clever-1 can inactivate activated T cells. In the context of autoimmune disease, you have T cells attacking your own tissue, for example, a joint or the bowel, and soluble Clever-1 could inactivate them. Using soluble Clever-1 against autoimmune diseases could be a very viable option. Soluble Clever-1 is, however, a very large molecule. You can't really manufacture it in a stable way. We're currently working on a construct. Basically, in layman terms, the drug design on what that drug would look like so that it's stable, could be given, and inactivates T cells. When we have that compound or drug structure in hand, we'll take that actually to IND enabling studies. For the layman, IND means studies that will be needed so you can go into clinical development. Hopefully, we'll get the drug design still during this year and take it to IND enabling studies next year, and following that into the clinic. Perfect. Anything from you, Petri? Sorry. Yeah, nothing to add after that. Since we are not yet at the IND stage, so it's not in the clinical pipeline at the moment, we are studying translational studies all the time. Soluble Clever-1, there's a publication out that it is prognostic in cancer patients. It was prognostic also in Matthews patients. The predictive role is something also we want to study. At the moment, MDS, we see wide activity of bexmarilimab, and we are not aiming to use, for example, soluble Clever-1 as a biomarker for patient selection in MDS. The upcoming registration trial is for all comers. Wonderful. Thank you very much for your time today, team. Absolutely great to hear from you all. Thank you all online for attending and asking such great questions. It was a real pleasure to meet you all, and hopefully see you again very soon. Thanks a lot.